No abstract

FDA-approved self-emulsifying medicines rely on liquid-based formulations, which can exhibit limited stability and short shelf-lives. Solid self-emulsifying drug delivery systems (SEDDS) can improve such issues, but there is still a great need for identifying suitable porous carriers to convert liquid SEDDS into solids without impairing their mechanical properties, functionality, and industrial feasibility. The impact of SEDDS adsorption on tableting is also poorly understood. Therefore, solid SEDDS were prepared by adsorbing liquid SEDDS onto ten commercially available porous excipients. Products were assessed with respect to mechanical behavior, tabletability, and product performance. Adsorbing SEDDS onto porous excipients led to satisfactory stability, with the exception of Zeopharm® 600 due to its high alkalinity, and Neusilin® US2/UFL2, which caused quercetin to crystallize out of the liquid concentrate. SEDDS adsorption reduced the elastic recovery of most excipients, making tableting achievable using Aeroperl® 300 and Aerosil® 200/300. The impact of SEDDS on elastic recovery provides additional understanding on solid SEDDS manufacture process. Acceptable tablets were made via direct compression but with slow disintegration. Addition of a superdisintegrant (crospovidone 5% w/w) ensured tablet manufacturing without impairment of product performance. Solid SEDDS displayed several technical advantages over their liquid counterparts, but attention must be given to the properties of the porous excipient chosen. Drug-excipient interactions play a significant role in drug degradation and crystallization in solid SEDDS. Improved mechanical behavior upon adsorption led to well-composed tablets that performed satisfactorily in vitro upon addition of a superdisintegrant. This study provides an insight on excipient-oriented rational development of solid SEDDS.

No abstract

Bulk solutions of therapeutic proteins are often frozen for long-term storage. During the freezing process, proteins in liquid solution redistribute and segregate in the interstitial space between ice crystals. This is due to solute exclusion from ice crystals, higher viscosity of the concentrated solution, and space confinement between crystals. Such segregation may have a negative impact on the native conformation of protein molecules. To better understand the mechanisms, we developed a phase-field model to describe the growth of ice crystals and the dynamics of freeze concentration at the mesoscale based on mean field approximation of solute concentration and the underlying heat, mass and momentum transport phenomena. The model focuses on evolution of the interfaces between liquid solution and ice crystals, and the degree of solute concentration due to partition, diffusive, and convective effects. The growth of crystals is driven by cooling of the bulk solution, but suppressed by a higher solute concentration due to increase of solution viscosity, decrease of freezing point, and the release of latent heat. The results demonstrate the interplay of solute exclusion, space confinement, heat transfer, coalescence of crystals, and the dynamic formation of narrow gaps between crystals and Plateau border areas along with correlations of thermophysical properties in the supercooled regime.

The purpose of the present study was to develop guidance toward rational choice of blenders and processing conditions to make robust and high performing adhesive mixtures for dry-powder inhalers and to develop quantitative experimental approaches for optimizing the process. Mixing behavior of carrier (LH100) and AstraZeneca fine lactose in high-shear and low-shear double cone blenders was systematically investigated. Process variables impacting the mixing performance were evaluated for both blenders. The performance of the blenders with respect to the mixing time, press-on forces, static charging, and abrasion of carrier fines was monitored, and for some of the parameters, distinct differences could be detected. A comparison table is presented, which can be used as a guidance to enable rational choice of blender and process parameters based on the user requirements. Segregation of adhesive mixtures during hopper discharge was also investigated.